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首页> 外文期刊>British Journal of Haematology >Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all-trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2
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Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all-trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2

机译：Epigallocatechin-3-gallate诱导急性髓样白血病细胞死亡，并通过死亡相关的蛋白激酶2支持全反式维甲酸诱导的中性粒细胞分化。

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SummaryAcute promyelocytic leukaemia (APL) patients are successfully treated with all-trans retinoic acid (ATRA). However, concurrent chemotherapy is still necessary and less toxic therapeutic approaches are needed. Earlier studies suggested that in haematopoietic neoplasms, the green tea polyphenol epigallocatechin-3-gallate (EGCG) induces cell death without adversely affecting healthy cells. We aimed at deciphering the molecular mechanism of EGCG-induced cell death in acute myeloid leukaemia (AML). A significant increase of death-associated protein kinase 2 (DAPK2) levels was found in AML cells upon EGCG treatment paralleled by increased cell death that was significantly reduced upon silencing of DAPK2. Moreover, combined ATRA and EGCG treatment resulted in cooperative DAPK2 induction and potentiated differentiation. EGCG toxicity of primary AML blasts correlated with 67 kDa laminin receptor (67LR) expression. Pretreatment of AML cells with ATRA, causing downregulation of 67LR, rendered these cells resistant to EGCG-mediated cell death. In summary, it was found that (i) DAPK2 is essential for EGCG-induced cell death in AML cells, (ii) ATRA and EGCG cotreatment significantly boosted neutrophil differentiation, and 67LR expression correlates with susceptibility of AML cells to EGCG. We thus suggest that EGCG, by selectively targeting leukaemic cells, may improve differentiation therapies for APL and chemotherapy for other AML subtypes.
机译：总结急性早幼粒细胞白血病（APL）患者已成功用全反式维甲酸（ATRA）治疗。然而，同时进行化疗仍然是必要的，并且需要毒性较小的治疗方法。较早的研究表明，在造血肿瘤中，绿茶多酚表没食子儿茶素-3-没食子酸酯（EGCG）诱导细胞死亡，而对健康细胞没有不利影响。我们旨在破译在急性髓细胞性白血病（AML）中EGCG诱导的细胞死亡的分子机制。在EGCG处理后，AML细胞中发现了死亡相关蛋白激酶2（DAPK2）的水平显着增加，与此同时，随着DAPK2沉默的降低，细胞死亡增加了。此外，ATRA和EGCG联合治疗可导致DAPK2协同诱导和增强分化。原发性AML母细胞的EGCG毒性与67 kDa层粘连蛋白受体（67LR）表达相关。用ATRA预处理AML细胞，导致67LR的下调，使这些细胞对EGCG介导的细胞死亡具有抗性。总而言之，发现（i）DAPK2对于EGCG诱导的AML细胞在AML细胞中的死亡是必不可少的，（ii）ATRA和EGCG的共同处理显着促进了嗜中性粒细胞的分化，并且67LR表达与AML细胞对EGCG的敏感性相关。因此，我们建议通过选择性靶向白血病细胞，EGCG可能会改善APL的分化治疗和其他AML亚型的化疗。

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